Objective:
The protective dose of the Human Adenovirus 5-Foot-and-Mouth Disease (Ad5-FMD) vaccine is high even when using an adjuvant to increase potency. In addition studies show that swine are not protected against Foot-and-Mouth Disease Virus (FMDV) with the vaccine when given the same protective dose as cattle. This collaborative research project seeks to improve the potency of the Ad5-Blue FMD vaccine through the following specific objectives:
1. Evaluation of alternative routes for vaccine delivery.
2. Evaluation of new adjuvants to use with the Ad5-FMD vaccine.
3. Improvement of the Ad5-Blue system; Vector modifications to prevent recombination.
4. Assessment of immune function following vaccination of swine with Ad5-FMD.

Approach:
1. Evaluation of alternative routes for vaccine delivery will be achieved through an assessment of the subcutaneous delivery of Ad5-FMD and an assessment of the intra/transdermal delivery utilizing a commercially available needle free delivery system as well as the evaluation of the biodistribution of Ad5 vector and transgene products in swine.
2. The Ad5-FMD vaccine developed to use alone or in combination with the biotheraputic/adjuvant Ad5-poIFNA alpha demonstrated protection as early as 1 day and for approximately 5 days post vaccination and enhanced long-term immunity. The potency of Ad5-A24-2B vaccine in combination with adjuvants inclusive of polyICLC and others will be evaluated. A lead adjuvant candidate will be selected for further studies in swine.
3. To improve the Ad5-Blue system the following vector modification studies will be performed: A. Determination of stability of transgene expression after repeated passage of Ad5-A24-2B. B. Modification to Ad5 capsids that target immune cells. C. Modifications to Ad5-FMD construct to include additional non-structural proteins. D. The capsid sequence of Ad5-FMD will be modified to increase expression, stability and cross-reactivity. E. Modification to the vectors to include new promoter and multicloning sites. F. Modification to the vectors to include capsid and interferon as adjuvants. G. Modifications to the vectors to deliver double-stranded RNA as innate response inducers. H. Construction of modified Ad5-Blue to reduce recombination and reversion to virulence and to broaden tropism and improve performance.
4. An assessment of the immune response following vaccination with Ad5-FMD in swine will be conducted through: A. An analysis of the antibody response of swine and the identification of qualitative differences of the serological induced response. B. The development of a combined Ad5-FMD vaccination strategy to induce both cellular and adaptive immunity through enhanced cytotoxic T cell response. C. Conducting microarray analysis in multiple tissues to assess swine response to FMDV vaccination.